Astatine-211-labeled biotin conjugates resistant to biotinidase for use in pretargeted radioimmunotherapy.
We report herein the preparation and biological evaluation of two radioastatinated biotin conjugates, (3-[211At]astatobenzoyl)norbiotinamide and ((5-[211At]astato-3-pyridinyl)carbonyl)norbiotinamide. Both conjugates were stable in the presence of human serum and cerebrospinal fluid as well as murine serum, indicating a resistance to degradation to biotinidase. The normal tissue clearance of (3-[211At]astatobenzoyl)norbiotinamide and ((5-[211At]astato-3-pyridinyl)carbonyl)norbiotinamide was rapid, as observed previously with their iodo analogues. Also reported are the first syntheses of N-succinimidyl 5-[211At]astato-3-pyridinecarboxylate and 3-[211At]astatoaniline, two reagents of potential utility for labeling proteins and peptides with 211At.
Foulon
C F
CF
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA. cfoulon@duke.edu
Alston
K L
KL
Zalutsky
M R
MR
D000581:Amidohydrolases / Q000134:cerebrospinal fluid / Q000737:chemistry*; D000818:Animals; D001246:Astatine; D001710:Biotin / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000138:chemical synthesis / Q000737:chemistry*; D043523:Biotinidase; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016499:Radioimmunotherapy; D011868:Radioisotopes; D019275:Radiopharmaceuticals / Q000134:cerebrospinal fluid / Q000737:chemistry*; D019809:Streptavidin / Q000737:chemistry; D014018:Tissue Distribution
C111113:((5-astato-3-pyridinyl)carbonyl)norbiotinamide; C111112:(3-astatobenzoyl)norbiotinamide; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D001710:Biotin; D019809:Streptavidin; D000581:Amidohydrolases; D043523:Biotinidase; D001246:Astatine